Biological Effects of Ionizing Radiation Module 8 - AAPM/RSNA Curriculum Basic Radiation Biology Kalpana M. Kanal, PhD, DABR Associate Professor, Radiology Director, Resident Physics Education a copy of this lecture may be found at: http://courses.washington.edu/radxphys/index.html UW and Kalpana M. Kanal, PhD, DABR 1
Why does a radiologist need to understand radiation biology? Assess the risk-benefit value from radiological and interventional procedures (increased number of radiation injuries to skin) Explain these risks to your colleagues and their patients The explosive growth in the use of computed tomography, nuclear imaging and other procedures has increased the radiation dose to the population The irradiation of the pregnant patient, either accidentally or intentionally, is another area where radiobiology is important in everyday practice An understanding of radiobiology, like an understanding of medical physics, gives radiologists another tool to add value to their practice 2
Radiation exposure to US population from all sources The new pie chart! US 1982 (NCRP 93) US 2006 (NCRP 160) Consumer products 2% Occupational 0.3% Consumer products 2% Occupational 0.1% Medical 15% Medical 48% Background 83% Background 50% Medical 0.54 msv per capita Total 3.6 msv per capita Medical 3.0 msv per capita Total 6.2 msv per capita UW and Kalpana M. Kanal, PhD, DABR Slide courtesy: Dr. M. Mahesh, Johns Hopkins
How are Biologic Effects Classified? Stochastic Effect The probability of the effect, rather than its severity, with dose Radiation-induced cancer and genetic effects Basic assumption: risk with dose and no threshold The principal health risk from low-dose radiation 4
How are Biologic Effects Classified? Deterministic or Non-stochastic Effect Severity of the effect, rather than its probability, with dose Requires much higher dose to produce an effect Threshold dose below which the effect is not seen Cataracts, erythyma, fibrosis, and hematopoietic damage are some deterministic effects Dx radiology: only observed in some lengthy, fluoroscopically guided interventional procedures, CT perfusion (if not done carefully) 5
How does Radiation Interact with Tissue? c.f. Bushberg, et al. The Essential Physics of Medical Imaging, 2 nd ed., p. 816. 6
Cell Cycle In radiation therapy differences in the length of the cell cycle for tumors and normal tissues are important Cells are most radiosensitive in M They are relatively more sensitive in late G2 Least sensitive in S The length of the cycle for quickly dividing mammalian cells is about 24 hours c.f. RSNA/AAPM Web Module on Basic Radiation Biology 7
Sensitivity of Cells Law of Bergonié and Tribondéau: applies to most but not all cells The sensitivity of cells is directly proportional to their reproductive activity and inversely proportional to their degree of differentiation Resistant Cells Sensitive Cells Cartilage Epithelium of the GI tract Bone Hematopoietic tissues Liver Basal cells Nervous tissue Germinal cells Kidney Lymphoid tissues Muscle 8
Sensitivity of Cells Exception: Peripheral lymphocytes are quite sensitive to radiation even though they are quite differentiated and do not divide. The peripheral lymphocyte count is used as a method to triage the severity of acute radiation exposure. c.f. RSNA/AAPM Web Module on Basic Radiation Biology 9
Cell Survival Curves c.f. RSNA/AAPM Web Module on Basic Radiation Biology 10
Cell Survival Curves c.f. RSNA/AAPM Web Module on Basic Radiation Biology 11
Cell Survival Curves c.f. RSNA/AAPM Web Module on Basic Radiation Biology 12
Cell Survival Curves The radiation dose necessary to kill about 90% of the cells in the population is: A) 1Gy B) 7Gy C) 10Gy D) 20Gy c.f. RSNA/AAPM Web Module on Basic Radiation Biology 13
Review Question NCRP 160 estimates that the average US population dose from medical exposure is about of that from background sources. A) 1/10 B) ½ C) Equal D) 2 E) 10 14
Review Question Deterministic or non-stochastic effects of radiation include all of the following except: A) Bone marrow damage B) Skin damage C) Cataract induction D) Leukemia E) Infertility due to gonadal irradiation 15
Review Question Stochastic effects of radiation (A) Can be recognized as caused by radiation (B) Have a dose-dependent severity (C) Have a threshold of 50 msv/year (D) Include carcinogenesis (E) Involve cell killing 16
JCAHO Sentinel Event c.f. Balter et al, Radiology 254(2), 326, Feb. 2010
Review Question Cells that are quite resistant to radiation are A) Lymphocytes B) Basal cells C) Muscle cells D) Hematopoietic cells 18
Review Question A skin dose of 3 Gy could lead to A) Transient erythema B) Permanent epilation C) Wet desquamation D) Skin necrosis 19
Skin Injuries Case Reports Two key articles from the American Journal of Roentgenology provide important background for the understanding of skin effects: Skin Injuries from Fluoroscopically Guided Procedures: Part 1, Characteristics of Radiation Injury. Koening, TR, Wolff, D., Mettler, FA, Wagner, LK., AJR 177, 3-11, 2001. Skin Injuries from Fluoroscopically Guided Procedures: Part 2, Review of 73 Cases and Recommendations for Minimizing Dose Delivered to Patient. Koening, D., Mettler, FA, Wagner, LK., AJR 177, 13-20, 2001 Balter article referenced below c.f. Balter et al, Radiology 254(2), 326, Feb. 2010 20
Skin Injuries Degree of skin injury Factor Time Patient thickness Distance to x-ray port kv ma Effect Increases linearly with time Increases exponentially with thickness Decreases as the square of the distance Decreases with increasing kv Increases linearly with ma ACCF/AHA/HRS/SCAI Clinical Competence Statement on Physician Knowledge to Optimize Patient Safety and Image Quality in Fluoroscopically Guided Invasive Cardiovascular Procedures : A Report of the American College of Cardiology Foundation/American Heart Association/American College of Physicians Task Force on Clinical Competence and Training: http://circ.ahajournals.org/content/111/4/511.short 21
Skin Injuries Case Reports c.f. Balter et al, Radiology 254(2), 326, Feb. 2010 22
CT Perfusion Over Exposure Hair loss after a CT perfusion scan Dose estimate of 4-5 Gy Hair loss after a CT perfusion scan to detect a possible stroke.
Organ Systems Response: Reproductive Organs Gonads are very radiosensitive Females Males Temporary sterility: 1.5 Gy acute dose Permanent sterility: 6.0 Gy acute dose* *reported for doses as low as 3.2 Gy Temporary sterility: 2.5 Gy acute dose* *reported for doses as low as 1.5 Gy Permanent sterility: 5.0 Gy acute dose Reduced fertility 20-50 mgy/wk when total dose > 2.5 Gy 24
Organ Systems Response: Ocular Effects Eye lens contains a population of radiosensitive cells Unlike senile cataracts that typically develop in the anterior pole of the lens radiation-induced cataracts begin with a small opacity in the posterior pole and migrate anteriorly Based on studies of patients and occupational workers, the International Commission on Radiological Protection (ICRP) recently released a statement indicating lens opacities occur at doses of 0.5 Gy 25
Organ Systems Response: Ocular Effects This threshold dose is much lower than previously thought Studies also show that the threshold dose for lens opacities does not change if the dose is received chronically over many years or acutely, as in patient exams Current ICRP Dose Threshold 0.5 Gy for acute and chronic exposure with latent period inversely related to dose Previous Lens Dose Thresholds 4 Gy for acute exposure with a latent period of ~ 4yrs 8 Gy for chronic exposure with a latent period from 8-35 years 26
Acute Radiation Syndrome (ARS) Characteristic clinical response when whole body (or large part thereof) is subjected to a large acute external radiation exposure Organism response quite distinct from isolated local radiation injuries such as epilation or skin ulcerations Combination of subsyndromes occurring in stages over hours to weeks as the injury to various tissues and organs is expressed In order of their occurrence with increasing radiation dose: Hematopoietic syndrome Gastrointestinal syndrome Neurovascular syndrome Acute Radiation Syndrome: A Fact Sheet for Physicians http://www.bt.cdc.gov/radiation/arsphysicianfactsheet.asp 27
ARS Summary c.f. Bushberg, et al. The Essential Physics of Medical Imaging, 2 nd ed., p. 837. 28
LD 50/60 LD 50/60 means the dose that would kill 50% of the exposed individuals within 60 days The LD 50/60 for humans is somewhere between 3.5 and 7 Gy depending on the level of care 29
Diagnosis and Treatment of Radiation Injuries Radiation injury is a complex medical event. Accidents are rare so most physicians will seldom see a case. Physicians should be able to diagnose and triage patients so appropriate care can be delivered. The IAEA Report on the diagnosis and treatment of radiation injuries can be found here: http:\\www-pub.iaea.org/mtcd/publications/pdf/p040_scr.pdf 30
Diagnosis and Treatment of Radiation Injuries Clinical Signs Dose (Gy) Decision Whole Body (WB) Local Exposure (LE) WB LE No vomiting No early erythema <1 <10 Outpatient with five weeks of general surveillance Vomiting two to Early erythema 12 1-2 8-15 Surveillance and a general three hours after to 24 hours after hospital for three weeks exposure exposure Vomiting in one to two hours after exposure Vomiting in less than one hour, or other severe symptoms Early erythema 8 to 15 hours after exposure Early erythema within the first 3 to 6 hours after exposure 2-4 15-30 Hospitalization in a hematological or surgical burn department >4 >30 Hospitalization with transfer to a specialized radiation management center 31
Review Question Which cells are considered to be the most radioresistant? (A) Bone marrow cells (B) Lymphoid tissues (C) Neuronal cells (D) Skin cells (E) Spermatids 32
Review Question A patient is brought to the hospital with an estimated whole body dose of 4 Gy. The most likely radiation syndrome would be A) Bone Marrow Syndrome B) Gastrointestinal Syndrome C) Central Nervous System Syndrome 33
Review Question Skin ulcers are most commonly seen A) Following CT B) Following GI fluoroscopy C) Following interventional neurological procedures D) Following interventional cardiac procedures 34